In patients with Bartter's syndrome (hypokalemic alkalosis, hyperreninemia, aldosteronism, increased adrenergic nervous system function, hyperprostaglandinuria, normal blood pressure) cyclic AMP content in platelet-rich plasma is supranormal and platelet aggregation is defective. It has been proposed that a stable prostaglandin (PG) related to prostacyclin, which is overproduced in Bartter's syndrome and is a potent antiaggregatory substance, is responsible for stimulation of cyclic AMP formation and impaired platelet aggregation. Evaluation of the production of cyclic AMP by platelets in Bartter's syndrome and in normal subjects showed that in vitro basal, PGE1-stimulated, and PGE1-stimulated, norepinephrine-inhibited cyclic AMP production by platelets in Bartter's syndrome was subnormal. The affinity of and binding by platelet alpha (alpha) receptors was normal. Treatment with indomethacin, an inhibitor of prostaglanding synthesis corrected only basal cyclic AMP production. These results indicate that in Bartter's syndrome cyclic AMP production by platelets is impaired and suggest that platelets are not the source of the increased plasma cyclic SSMP concentration that probably decreases platelet aggregation in this disorder.